Gastric Cancer Screening in Common Variable Immunodeficiency

Abstract

Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.

Consensus of the Italian Primary Immunodeficiency Network on transition management from pediatric to adult care in patients affected with childhood-onset inborn errors of immunity

“…Up to 20% of adult patients with CVID develop cancer, 21,[31][32][33][34] including malignancies of lymphatic tissue, such as non-Hodgkin lymphoma and gastrointestinal cancer, which is almost 50 times more frequent than in the healthy population. 21,[35][36][37] Gastrointestinal tract malignancies (eg, gastric adenocarcinoma, liver carcinoma, colon adenocarcinoma) have been reported in patients with XLA. 11,38,39 Group-specific consensus.…”

From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency

“…Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer[ 50 ]. A gastric screening protocol was proposed[ 51 ]. This is to include a gastroscopy in individuals with CVID with any of the following risk factors: Age greater than 50, CVID diagnosis since more than 10 years, significant smoking history, family history of gastric carcinoma, persistent diarrhea or upper gastrointestinal symptoms, previous gastroscopy with inadequate biopsies, positive Helicobacter pylori breath test, iron deficiency, and low serum vitamin B12.…”

“…As CVID patients also have an increased risk of gastrointestinal lymphoma, it seems reasonable to perform multiple biopsies from the gastric antrum and body and additionally from the second part of the duodenum. It is reported that fewer biopsies decreased the probability of detecting early premalignant lesions[ 51 ]. Dhalla et al[ 52 ] suggested to perform upper endoscopy with an interval between the subsequent endoscopic assessment based on histological findings: Every 1–3 years in patients with metaplasia, every 3 years in patients with atrophic gastritis, and every 6–12 mo in those with dysplasia.…”

State-of-the-art diagnostic evaluation of common variable immunodeficiency

“…40 Other studies have revealed that general screening of patients with CVID can lead to early detection of GI pathology in as high as 80%, including intestinal metaplasia, atrophic gastritis, collagenous gastritis, giardiasis, duodenal villous atrophy, and intraepithelial lymphocytosis. 41 Biopsies taken from the GI mucosa can reveal excess intraepithelial lymphocytes, villous blunting, lymphoid aggregates, granulomas, crypt distortion, and a lack of plasma cells. 38,42 However, the clinical significance of these findings remains to be fully revealed.…”